Recently a number of laboratories have studied the effect of ethanol on the ability of the liver to regenerate in vivo showing that chronic administration of ethanol inhibits 3H thymidine incorporation into DNA following partial hepatectomy. More specifically ethanol has been shown to inhibit hepatocyte DNA synthesis following hormonal stimulation by a number of agents including epidermal growth factor (EGF). However, at a cellular level many unanswered questions concern the mechanism of action of various growth factors. We have previously shown that in hypophysectomized animals GH is unique among the hormones tested by causing an increase in the [NADP+]/[NADPH] ratio in liver. (This is relevant when considering the metabolic effects of ethanol, as another study has shown a transient decrease in the [NADP+]/[NADPH] ratio in liver following ethanol administration.) In an attempt to understand the mechanism by which ethanol interferes with the normal processes of growth and development, we have undertaken an extensive study on the early metabolic changes induced by several hormones and growth factors in vivo. In addition, we have demonstrated a direct effect of ethanol on the normal metabolic action of EGF in vivo. Continuing studies are in progress to further elucidate (a) the mechanisms of growth factor action in vivo, (b) the ethanol related interactions with these processes.